With a majority of the more than 100,000 million dental restorative treatments performed in the US each year involving the placement of resin-bonded composite materials, and the acknowledgement that a large portion of a dentist's time is consumed with revising and replacing these restorations, there is a clear need for materials with improved clinical performance. Composite restoratives not only hold an esthetic advantage over dental amalgams, but they offer a means to adhesively bond the restoration to dentin and enamel. However, due to challenges imposed by wet bonding techniques, the potential for water-induced phase separation prior to, during or over extended intervals following polymerization of this critical interface, a strong, intact margin cannot currently be reliably obtained. This proposal describes the development plan for new water compatible monomers that compared with HEMA, offer the potential for improved reactivity, avoidance of phase separation and the production of chemically and mechanically sound polymer networks. A highly versatile technique has been developed for preparing nano-scale (10 - 30 nm) polymeric particles with control over branching, chemistry and reactive site placement. These reactive nanogels can be dispersed readily at high concentrations in secondary monomers, which then infiltrate and subsequently copolymerize with the prepolymer additives. The proposed project is constructed around three specific aims: 1) water-compatible monomers as alternatives to or in addition to HEMA will be developed as a means to better maintain homogeneity and high crosslink densities throughout adhesive resins; 2) the positive preliminary results with nanogel-modified adhesives will be extended into water-dispersible reactive nanogels that provide enhanced structural homogeneity and stability while introducing components that cannot be dispersed in water as free monomers; and 3) micro/nano-mechanical property characterization coupled with imaging of the adhesive layer and interfaces will be collectively used as an analytical tool to better understand structure and properties associated with the interaction between dentin and the adhesive resin in existing materials as well as the advanced adhesives proposed here. We expect to correlate the stabilization of the adhesive resin phase with collagen protection strategies that include collagen crosslinking, anti-bacterial activity and MMP-inhibiting properties based on the non-migrating nanogel platform. The application will provide an improved understanding of the strengths and weaknesses of existing adhesive systems, while developing new materials that address the significant current problems of structural stability and durability within the adhesive and hybrid layers of bonded dental restorations.